Heterogeneous multimodal breast phantom

ABSTRACT

A heterogeneous patient-based breast phantom that mimics the anatomy and properties of real breast tissues when screened with ionizing and nonionizing imaging modalities is described. The heterogeneous breast phantom includes a skin mimicking segment; an adipose tissue mimicking segment; a fibro-glandular tissue mimicking segment; and a pectoral muscle mimicking segment wherein each segment is shaped and arranged such that the breast phantom represents a breast tissue. Performance of the breast phantom was characterized by mass attenuation coefficient, electron density and effective atomic number. Further, performance of breast phantoms was confirmed CT and breast MM machines.

STATEMENT OF FUNDING ACKNOWLEDGEMENT

This project was funded by the Deanship of Scientific Research, ImamAbdulrahman Bin Faisal University through grant number 2020-053-Eng.

STATEMENT REGARDING PRIOR DISCLOSURE BY THE INVENTORS

Aspects of this technology are described in “Heterogeneous BreastPhantom with Carcinoma for Ionizing Machines” presented at the IEEEIEMTRONICS 2021 conference on Apr. 21, 2021, which is incorporatedherein by reference in its entirety.

BACKGROUND Technical Field

The present disclosure is directed to heterogeneous breast phantomswhich can be applied to various breast imaging modalities for thedetection of early cancer and lesions. The heterogeneous breast phantommimics the real breast tissues in terms of anatomy and tissue propertiesconcerning the conventional breast imaging techniques.

Description of Related Art

The “background” description provided herein is for the purpose ofgenerally presenting the context of the disclosure. Work of thepresently named inventors, to the extent it is described in thisbackground section, as well as aspects of the description which may nototherwise qualify as prior art at the time of filing, are neitherexpressly or impliedly admitted as prior art against the presentinvention.

The existing medical imaging phantoms have a lot of limitationsincluding unrealistic uniform background structure that does not mimicreal organs and tissues. They are mostly designed with homogeneous (ofthe same properties everywhere in the phantom) solutions for the wholeaimed organ with no accurate simulation of tumors, masses or otherlesions. Additionally, most of the breast phantoms are tailored tofunction with a single imaging modality by simulating the tissuematerial response only for this single modality considering QualityAssurance (QA) only.

Breast cancer is the second most occurring cancer in females andconsidered as the second reason of mortality as described in Anon., Sep.14, 2020, https_://www.cdc.gov/cancer/breast/basic_info/index.htm, theentire disclosure is incorporated by reference. Based on the nationalbreast cancer foundation, an estimation of 276 thousand new cases werediagnosed with breast cancer in 2020 and more than 42 thousand women areexpected to die in the United States (US) as described by Anon., Nov.26, 2020,https_://www.nationalbreastcancer.org/wpcontent/uploads/2020-Breast-Cancer-Stats.pdf,the entire disclosure is incorporated herein by reference. However,early stage cancer detection would increase treatment possibilities andthe survival rate as described by Anon., Nov. 26, 2020,https_://www.who.int/activities/promoting-cancer-early-diagnosis, theentire disclosure is incorporated herein by reference. Breast phantomsare significant devices that help in early breast cancer detection. Theymust mimic the properties of the breast tissues with tissue equivalentmaterials having similar response of the breast when it is screened byeach imaging modality. Anthropomorphic breast phantoms are utilized toproduce images that simulate aspects of clinical breast screening. Theyare beneficial in characterization and optimization of breast imagingmodalities. In the development of imaging screening technologies,technical assessment for modality optimization through phantoms isessential before the modality can be utilized for clinical use.Nowadays, the existing medical imaging phantoms have a lot oflimitations including unrealistic uniform background structure that doesnot mimic real organs and tissues. They are mostly designed withhomogenous solutions for the whole aimed organ with no simulation oftumors, masses, or other lesions.

Phantoms are devices that are being used in the field of medical imagingphysics and health science as described by DeWerd and Lawless in“Introduction to Phantoms of Medical and Health Physics,” in ThePhantoms of Medical and Health Physics: Devices for Research andDevelopment, L. A. DeWerd and M. Kissick, Eds. New York, N.Y.: Springer,2014, pp. 1-14, the entire disclosure is incorporated herein byreference. They are considered as artificial models that represent thehuman body to evaluate, examine and tune the performance of severalimaging modalities. Phantoms are designed to help in assessing theoptimal radiation that is subjected to the patient especially in newemerging imaging techniques and for quality assurance (QA) purposes.Such advanced phantoms that are patient-based can further benefit inhands-on operator training and image-guided interventional procedures.Based on the purpose that the phantom is developed for, the compositionand the design process would be established.

In 2015, a group at Duke University developed a breast phantom bymatching virtual breast phantoms for mammography projections. Thevirtual phantoms were made into physical phantoms using additivemanufacturing multilateral 3D printing. One design was printed withsingle additive materials then filled with oil. Second design was madewith double additive printed materials for whole breast. The secondphantom design offered a better result in term of breast contrastcompared to the first design, but the second presented undesirable airbubbles as described by Kiarashi et al. in “Development of realisticphysical breast phantoms matched to virtual breast phantoms based onhuman subject data”, Medical Physics, vol. 42, no. 7, pp. 4116-4126,2015., the entire disclosure is incorporated herein by reference.

Another physical 3D anthropomorphic breast phantom was developed at theUniversity of Pennsylvania for image quality assessment of 2D and 3Dbreast x-ray imaging systems. The fabricated phantom consists of 45%dense tissue and already 5 cm deformed in thickness for mammographyscan. Digital mammographic images with W/Rh at 30 kVp and 104 mAs showeda less than 1% coefficient of variation of the relative attenuationbetween the two simulated tissues with acceptable appearance withpresence of air bubbles as described by Carton et al. in, “Developmentof a physical 3D anthropomorphic breast phantom,” Med. Phys., vol. 38,no. 2, pp. 891-896, 2011, the entire disclosure is incorporated hereinby reference.

Moreover, another method for fabricating breast phantoms was developedby a research group at the Committee for the defense of human right(CDHR). The aim was to model breast X-ray attenuation properties. Thephantom was designed only to match full-field digital mammography (FFDM)and digital breast tomosynthesis (DBT). After projections at 35 kVp itwas found that both glandular and adipose tissues were acceptable withlimitation of masses and lesions insertion to the phantom as describedby Rossman et al. in “Three dimensionally-printed anthropomorphicphysical phantom for mammography and digital breast tomosynthesis withcustom materials, lesions, and uniform quality control region,” J. Med.Imaging Bellingham Wash, vol. 6, no. 2, p. 021604, Apr. 2019, the entiredisclosure is incorporated herein by reference.

A study was published with an aim to construct breast phantom made frompolyethylene by segmenting the patient's breast image into adipose andfibro-glandular tissues. To mimic the different tissues, thermoplasticmold was placed as the outer layer of the skin, fibro-glandular tissuewas represented by filling the air gaps with water, while polyethyleneand paraffin wax were used to mimic the adipose tissue. Moreover,calcium carbonate particles were used to represent themacrocalcification. The designed phantom model uncompressible breastwith an ability to do measurements as described by Prionas et al. in“Development of a Patient-Specific Two-Compartment AnthropomorphicBreast Phantom,” Phys. Med. Biol., vol. 57, no. 13, pp. 4293-4307, Jul.2012, the entire disclosure is incorporated herein by reference.

In 2016, a paper published with an aim to develop a multipurposegel-based breast phantom consisting of a simulated tumor to functionwith ultrasound, CT, and Magnetic Resonance Imaging (MRI). The TissueMimicking Material (TMMs) was ballistic gelatin powder and Metamusil forbreast background. Barium sulfate, copper sulfate, water and ballisticgelatin were used for the simulated tumor. The resulted Hounsfield units(HU) of the simulated breast background was 24 HU which was far from thereference value of −100 HU for adipose and 40 HU for fibro-glandular. OnMM, the tumor showed a signal-difference to noise ratio of 3.7 asdescribed by Ruschin et al. in, “Technical Note: Multipurpose CT,ultrasound, and MRI breast phantom for use in radiotherapy and minimallyinvasive interventions,” Med. Phys., vol. 43, no. 5, p. 2508, May 2016,the entire disclosure is incorporated herein by reference.

In 2019, a study was conducted to design a 3D-printed breast phantom formultimodal imaging with TMMs based on a 3D printing. The developedphantom was based on polyvinyl chloride (PVC) including a structure ofdifferent lesions, adipose, and fibro-glandular tissues. CT and MRI wereused to determine the tissue mimicking properties considering the HU andMRI relaxation times. The results showed that the temperature differencebetween the PVC softener mixture and the breast mold could presentbubbles that affects the image quality and cannot be eliminated. Also,lack of heterogeneity present in the tissues reduces the similarity tothe real breast tissues as described by He et al. in “3D-printed breastphantom for multi-purpose and multi-modality imaging,” Quant. ImagingMed. Surg., vol. 9, no. 1, pp. 63-74, Jan. 2019, the entire disclosureis incorporated herein by reference.

Recently in 2020, a group at Sapienza University published a phantom formultimodality use. The TMMs were based on different properties such asdielectric properties, acoustic properties, and attenuation coefficient.The phantom used TMMs to simulate the skin, fat tissue, glandulartissue, tumor, and muscle. The phantom resulted in a good match betweenthe reference and the physical measured values with ±10% for themajority of the TMMs. However, the phantom solid parts were compressionirreversible because of the fat layer composition. Also, furtherinvestigation would be necessary to have more contrast between the tumorand surrounding tissues as described by Ruvio et al. in “MultimodalBreast Phantoms for Microwave, Ultrasound, Mammography, MagneticResonance and Computed Tomography Imaging,” Sensors, vol. 20, no. 8,Art. no. 8, Jan. 2020, the entire disclosure is incorporated herein byreference.

Despite these recent efforts, there is still a need to developheterogeneous breast phantoms that effectively mimic real breasttissues.

SUMMARY

In an exemplary embodiment, a heterogeneous breast phantom is described.The heterogeneous breast phantom comprises a skin mimicking segment thatcomprises polyvinyl alcohol and sugar; an adipose tissue mimickingsegment that comprises beeswax; a fibro-glandular tissue mimickingsegment that comprises glycerol; and a pectoral muscle mimicking segmentthat comprises sugar and optionally comprises egg whites, wherein eachsegment is shaped and arranged such that the breast phantom represents abreast tissue.

In some embodiments, the heterogeneous breast phantom further comprisesa carcinoma mimicking segment that comprises sugar.

In some embodiments, each segment further comprises water, a vegetableoil, a surfactant, and agar.

In some embodiments, the vegetable oil is safflower oil.

In some embodiments, the surfactant is a nonionic surfactant.

In some embodiments, the skin mimicking segment, the adipose tissuemimicking segment, the fibro-glandular tissue mimicking segment, and thecarcinoma mimicking segment each further comprise at least one type ofscattering particles selected from the group consisting of NaCl, KCl,Al₂O₃, and SiC particles.

In some embodiments, polyvinyl alcohol and sugar are present in the skinmimicking segment in amounts of 4-6 wt. % and 27-35 wt. %, each relativeto a total weight of the skin mimicking segment.

In some embodiments, beeswax is present in the adipose tissue mimickingsegment in an amount of 38-45 wt. % relative to a total weight of theadipose tissue mimicking segment.

In some embodiments, glycerol is present in the fibro-glandular tissuemimicking segment in an amount of 10-15 wt. % relative to a total weightof the fibro-glandular tissue mimicking segment.

In some embodiments, sugar is present in the pectoral muscle mimickingsegment in an amount of 22-28 wt. % relative to a total weight of thepectoral muscle mimicking segment, and wherein egg whites, if present,are present in an amount of 2-8 wt. % relative to a total weight of thepectoral muscle mimicking segment.

In some embodiments, sugar is present in the carcinoma mimicking segmentin an amount of 20-25 wt. % relative to a total weight of the carcinomamimicking segment.

In some embodiments, the skin mimicking segment has an electron density(n_(e)) of 3.59E+23 −3.61E+23 e−/g and an effective atomic number(Z_(eff)) of 7.2-7.3.

In some embodiments, the adipose tissue mimicking segment has anelectron density (n_(e)) of 3.17E+23 −3.20E+23 e−/g and an effectiveatomic number (Z_(eff)) of 6.3-6.4.

In some embodiments, the fibro-glandular tissue mimicking segment has anelectron density (n_(e)) of 3.15E+23 −3.45E+23 e−/g and an effectiveatomic number (Z_(eff)) of 6.9-7.4.

In some embodiments, the pectoral muscle mimicking segment has anelectron density (n_(e)) of 3.40E+23 −3.5E+23 e−/g and an effectiveatomic number (Z_(eff)) of 8.1-8.3.

In some embodiments, the carcinoma mimicking segment has an electrondensity (n_(e)) of 3.25E+23 −3.65E+23 e−/g and an effective atomicnumber (Z_(eff)) of 7.1-7.5.

In some embodiments, the heterogeneous breast implant simulates thebreast tissue under a medical imaging technique.

In some embodiments, the medical imaging technique is magnetic resonanceimaging (MRI), computed tomography scan (CT scan), or both.

In yet another embodiment, a method of producing the heterogeneousbreast phantom is provided wherein the method comprises casting a firstcomposition that comprises polyvinyl alcohol and sugar to a skin-shapedmold, thereby forming the skin mimicking segment; casting a secondcomposition that comprises beeswax to an adipose tissue-shaped mold,thereby forming the adipose tissue mimicking segment; casting a thirdcomposition that comprises glycerol to a fibro-glandular tissue-shapedmold, thereby forming the fibro-glandular tissue mimicking segment;casting a fourth composition that comprises sugar and optionallycomprises egg whites to a pectoral muscle-shaped mold, thereby formingthe pectoral muscle mimicking segment; casting a fifth composition thatcomprises sugar to a carcinoma-shaped mold, thereby forming thecarcinoma mimicking segment; and, arranging the segments to produce theheterogeneous breast phantom such that the phantom represents a breasttissue.

In some embodiments, the method of producing the heterogeneous breastphantom is provided wherein at least one of the molds is produced via3-dimensional (3D) printing.

The foregoing general description of the illustrative embodiments andthe following detailed description thereof are merely exemplary aspectsof the teachings of this disclosure and are not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete appreciation of this disclosure and many of theattendant advantages thereof will be readily obtained as the samebecomes better understood by reference to the following detaileddescription when considered in connection with the accompanyingdrawings, wherein:

FIGS. 1A-1D are 3-dimensionl (3D) segmented models comparable to the MRIimage slices from different perspectives.

FIG. 2 is a 3D phantom molds design.

FIGS. 3A-3D show breast phantom molds: (FIG. 3A) outer skin, (FIG. 3B)skin, (FIG. 3C) fibro-glandular and (FIG. 3D) carcinoma mold.

FIG. 4 shows real and calculated skin elemental compositions photonenergy vs. mass attenuation coefficient graph.

FIG. 5 shows real and calculated Adipose elemental compositions photonenergy vs. mass attenuation coefficient graph.

FIG. 6 shows real and calculated fibro-glandular elemental compositionsphoton energy vs. mass attenuation coefficient graph.

FIG. 7 shows real and calculated carcinoma elemental compositions photonenergy vs. mass attenuation coefficient graph.

FIG. 8 shows real and calculated pectoral muscle elemental compositionsphoton energy vs. mass attenuation coefficient graph.

FIG. 9 shows fabrication methods for TMMs.

FIG. 10 shows measurement of T1 and T2 relaxation times of the TMMs.

FIG. 11 shows the fabricated breast phantom.

FIG. 12 shows validation of the phantom using clinical CT and breast MRIMachines.

FIG. 13 is a schematic flow diagram of a method of producing theheterogeneous breast phantom.

DETAILED DESCRIPTION

In the drawings, like reference numerals designate identical orcorresponding parts throughout the several views. Further, as usedherein, the words “a,” “an” and the like generally carry a meaning of“one or more,” unless stated otherwise.

Furthermore, the terms “approximately,” “approximate,” “about,” andsimilar terms generally refer to ranges that include the identifiedvalue within a margin of 20%, 10%, or preferably 5%, and any valuestherebetween.

The existing medical imaging phantoms have a lot of limitationsincluding unrealistic uniform background structure that does not mimicreal organs and tissues. They are mostly designed with homogeneous (ofthe same properties everywhere in the phantom) solutions for the wholeaimed organ with no accurate simulation of tumors, masses or otherlesions. Additionally, most of the breast phantoms are tailored tofunction with a single imaging modality by simulating the tissuematerial response only for this single modality considering QualityAssurance (QA) only.

The present invention provides a single heterogeneous breast phantom (ofdifferent materials mimicking tissues and hence properties) that can beapplicable to various imaging modalities with mimicking several breasttissues and carcinoma that can help in optimizing breast emergingsystems and assessing the optimal radiation that would be subjected tothe patient as well as QA purposes. In some embodiments, the inventivephantom offer advances in being patient-based developed, which canovercome the existing limitations in term of unrealistic structure.

In some embodiments, the invention is a heterogeneous anthropomorphicpatient-based multi-modality breast phantom that mimics the real breasttissues in terms of anatomy and tissue properties concerning theconventional breast imaging techniques. The structured tissues of thephantom concern the skin, fibro-glandular tissue, adipose tissue,pectoral muscle and carcinoma with new developed tissue mimickingmaterials (TMMs). The purpose of the TMMs was to match the response ofthe real breast tissues when applied to ionizing and non-ionizingimaging modalities. The designed phantom revealed excellent ionizingradiation properties as the real breast tissues. These properties werethe effective atomic number (Z_(eff)), electron density (ne) and massattenuation coefficient (MAC).

Moreover, the T1 and T2 relaxation times of the TMMs exhibited excellentagreement with the real breast tissues when examined at magneticresonance imaging (MRI) laboratory at 0.5 Tesla. The fabricated breastphantom was tested using computed tomography (CT) and MM machines, andthe scanned images were in excellent agreement with the real tissueswhen examined using these machines. Two carcinoma TMMs of 2-cm.diameters were inserted in the breast, and they appeared clearly in theCT scanned images. The two carcinoma TMMs were modeled as malignantwater content tissues and they appeared dark when T1-Weighted imagecontrast technique was used in MM and bright when T2-Weighted imagecontrast technique was used.

The achieved results were in great agreement with the real water contentcarcinoma tissues when examined with an MRI using T1W and T2W.

The present invention provides a heterogeneous breast phantom comprisinga skin mimicking segment that comprises polyvinyl alcohol and sugar; anadipose tissue mimicking segment that comprises beeswax; afibro-glandular tissue mimicking segment that comprises glycerol; and apectoral muscle mimicking segment that comprises sugar and optionallycomprises egg whites, wherein each segment is shaped and arranged suchthat the breast phantom represents a breast tissue.

In some embodiments, each segment further comprises water, a vegetableoil, a surfactant, and agar.

The skin mimicking segment may comprise polymers, including naturalpolymers and synthetic polymers, which mimic the skin of a real breast.Exemplary natural polymers include, without limitation, agarose (i.e.,agar), methylcellulose, and hyaluronan. Exemplary synthetic polymersinclude, without limitation, polyvinylpyrrolidone, polyvinyl alcohol,silicone (e.g., dimethicone, methicone, phenyl trimethicone, andcyclomethicone), polyacrylamide, polymacon, polyethylene oxide,poly(2-acrylamido-2-methyl-1-propanesulfonic acid), sodium polyacrylate,poly(hydroxyethyl methacrylate), polymethacrylate, polyethylacrylate,polyethylene terephthalate, polymethyl methacrylate, and copolymersthereof.

In preferred embodiments, the skin mimicking segment comprises polyvinylalcohol and agar. The polyvinyl alcohol employed in the skin mimickingsegment may have a weight average molecular weight from 20 kDa to 100kDa, 40 kDa to 80 kDa, or 50 kDa to 75 kDa.

Exemplary sugars that may present in the skin mimicking segment include,but are not limited to, lactose, sucrose, mannitol, and sorbitol.

In some embodiments, polyvinyl alcohol and sugar are present in the skinmimicking segment in amounts of 4-6 wt. % and 27-35 wt. %, each relativeto a total weight of the skin mimicking segment.

In some aspects of the invention, polyvinyl alcohol and sugar arepresent in the skin mimicking segment in amounts of 4, 4.5, 5.0, 5.5, or6 wt. % and 27, 28, 29, 30, 31, 32, 33, 34 or 35 wt. %, each relative toa total weight of the skin mimicking segment. Preferably, polyvinylalcohol is present in an amount of 5-5.5 wt % relative to a total weightof the skin mimicking segment. Preferably, sugar is present in an amountof 30-32 wt % relative to a total weight of the skin mimicking segment.

The skin mimicking segment may further comprise water, a surfactant(e.g., X-100 surfactant), an antimicrobial agent (e.g., quaternaryammonium salts such as benzalkonium chloride), and scattering particles.

The water used herein may be tap water, distilled water, bidistilledwater, deionized water, deionized distilled water, reverse osmosiswater, and/or some other water. Most preferably the water is deionizedwater.

Surfactants that may be present in the segments of the presentlydisclosed breast phantom include zwitterionic (amphoteric) surfactants,e.g., phosphatidylcholine, and3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS),anionic surfactants, e.g., sodium lauryl sulfate, sodium octanesulfonate, sodium decane sulfonate, and sodium dodecane sulfonate,non-ionic surfactants, e.g., Triton™ X (e.g., Triton™ X-100), IGEPALCA-630, Conco NI, Dowfax 9N, Igepal CO, Makon, Neutronyx 600's, NonipolNO, Plytergent B, Renex 600's, Solar NO, Sterox, Serfonic N, T-DET-N,Tergitol NP, Triton N, sorbitan monolaurate, sorbitan monopalmitate,sorbitan trioleate, polysorbates such as polysorbate 20 (Tween 20),polysorbate 60 (Tween 60), and polysorbate 80 (Tween 80), cationicsurfactants, e.g., decyltrimethylammonium bromide,dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide,tetradecyltrimethyl-ammonium chloride, and dodecylammonium chloride, andcombinations thereof. In preferred embodiments, the surfactant is anonionic surfactant. In a most preferred embodiment, the nonionicsurfactant is Triton™ X-100.

Preferably, the surfactant present in the skin mimicking segment is anon-ionic surfactant such as Triton™ X-100.

Antimicrobial agents that may be present in the segments of thecurrently claimed breast phantom include quaternary ammonium salts suchas benzalkonium chloride, benzethonium chloride, methylbenzethoniumchloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium,cetrimide, dofanium chloride, tetraethylammonium bromide,didecyldimethylammonium chloride, undecylenic acid, fluconazole,amphotericin B, sphingosine, and nystatin, triclosan, chlorhexidine,cetyl pyridinium chloride, benzethonium chloride, and bromochlorophene.

Preferably, the antimicrobial agent present in the skin mimickingsegment is benzalkonium chloride.

The segments of the currently claimed breast phantom may furthercomprise at least one type of scattering particles selected from thegroup consisting of NaCl, KCl, Al₂O₃, and SiC particles. Preferably, thescattering particles present in the skin mimicking segment are NaClparticles.

The adipose tissue mimicking segment may comprise a wax, preferablybeeswax, that mimics the adipose tissue of a real breast. In someembodiments, beeswax is present in the adipose tissue mimicking segmentin an amount of 38-45 wt. % relative to a total weight of the adiposetissue mimicking segment.

In certain aspects of the invention, beeswax is present in the adiposetissue mimicking segment in an amount of 38, 39, 40, 41, 42, 43, 44 or45 wt. % relative to a total weight of the adipose tissue mimickingsegment. Preferably, beeswax is present in an amount of 42-43 wt %relative to a total weight of the adipose tissue mimicking segment.

In some embodiments, other waxes including carnauba wax, jojoba wax, andsynthetic waxes may be used in addition to or in lieu of beeswax. Insome embodiments, the waxes may have melting point in a range of 60 to85° C. In certain examples, the waxes may have a melting point in arange of 62 to 82° C., 62 to 72° C., or 62 to 65° C.

The adipose tissue mimicking segment may further comprise water, agar, asurfactant, and scattering particles as defined above, and a vegetableoil. Preferably, the scattering particles present in the adiposemimicking segment are a mixture of NaCl, SiC, and KCl particles.

In some embodiments, vegetable oil, preferably safflower oil, may bepresent in segments of the breast phantom. In some embodiments, othervegetable oils such as olive oil, palm oil, rapeseed oil, soybean oil,corn oil, sunflower oil, cottonseed oil, peanut oil, grape seed oil,coconut oil, canola oil, or sesame oil may be used in lieu of or inaddition to the safflower oil. Preferably, the vegetable oil present inthe adipose tissue mimicking segment is safflower oil.

The fibro-glandular tissue mimicking segment may comprise a glycol, suchas ethylene glycol, diethylene glycol, triethylene glycol, tetraethyleneglycol, propylene glycol, dipropylene glycol, 1,3-propanediol,1,3-butanediol, 1,4-butanediol, 1,6-hexanediol, glycerol,pentaerythritol, manitol, and sorbitol. Preferably, the fibro-glandulartissue comprises glycerol. In some embodiments, glycerol is present inthe fibro-glandular tissue mimicking segment in an amount of 10-15 wt. %relative to a total weight of the fibro-glandular tissue mimickingsegment.

In certain aspects, glycerol is present in the fibro-glandular tissuemimicking segment in an amount of 10, 11, 12, 13, 14 or 15 wt. %relative to a total weight of the fibro-glandular tissue mimickingsegment. Preferably, glycerol is present in an amount of 12-13 wt %relative to a total weight of the fibro-glandular tissue mimickingsegment.

The fibro-glandular tissue mimicking segment may further comprise water,agar, a surfactant, an antimicrobial agent, scattering particles, and avegetable oil as defined above. Preferably, the scattering particlespresent in the fibro-glandular mimicking segment are a mixture of SiC,Al₂O₃, and KCl particles.

In some embodiments, sugar is present in the pectoral muscle mimickingsegment in an amount of 22-28 wt. % relative to a total weight of thepectoral muscle mimicking segment, and wherein egg whites, if present,are present in an amount of 2-8 wt. % relative to a total weight of thepectoral muscle mimicking segment.

In certain aspects, sugar is present in the pectoral muscle mimickingsegment in an amount of 22, 21, 22, 23, 24, 25, 26, 27 or 28 wt. %relative to a total weight of the pectoral muscle mimicking segment, andwherein egg whites, if present, are present in an amount of 2, 3, 4, 5,6, 7 or 8 wt. % relative to a total weight of the pectoral musclemimicking segment. Preferably, sugar is present in an amount of 25-27 wt% relative to a total weight of the pectoral muscle mimicking segment.Preferably, egg whites are present in an amount of 3-4 wt % relative toa total weight of the pectoral muscle mimicking segment.

The pectoral muscle tissue mimicking segment may further comprise water,agar, a surfactant, an antimicrobial agent, and a vegetable oil asdefined above.

In some embodiments, the heterogeneous breast phantom further comprisesa carcinoma mimicking segment that comprises sugar.

In some embodiments, sugar is present in the carcinoma mimicking segmentin an amount of 20-25 wt. % relative to a total weight of the carcinomamimicking segment.

In some embodiments, sugar is present in the carcinoma mimicking segmentin an amount of 20, 21, 22, 23, 24 or 25 wt. % relative to a totalweight of the carcinoma mimicking segment. Preferably, sugar is presentin an amount of 22-23 wt % relative to a total weight of the carcinomamimicking segment.

The carcinoma mimicking segment may further comprise water, agar, anantimicrobial agent, and scattering particles as defined above.Preferably, the scattering particles present in the carcinoma mimickingsegment are a mixture of NaCl and KCl particles.

Exemplary compositions of the skin mimicking segment, the adipose tissuemimicking segment, the fibro-glandular tissue mimicking segment, and thecarcinoma mimicking segment according to this invention are given inTables 1 through 5.

TABLE 1 Formula for the Skin Component Component Weight (g) SodiumChloride (NaCl) 15 Deionized Water 620 Triton X-100 Surfactant 30Polyvinyl alcohol (PVA) 50 Agar 5 Benzalkonium Chloride 4 Sugar 300

TABLE 2 Formula for Adipose Tissue Component Component Weight (g) SodiumChloride (NaCl) 2 Deionized Water 110 Triton X-100 Surfactant 100Safflower oil 315 Beeswax 400 Agar 7 Silicon Carbide (SiC) 4.9 PotassiumChloride (KCl) 6.5

TABLE 3 Formula for Fibro-glandular Tissue Component Component Weight(g) Silicone Carbide 4 Deionized Water 663.8 Triton X-100 Surfactant 40Safflower Oil 170 Glycerol 130 Agar 27 Aluminum oxide 15 PotassiumChloride (KCl) 5 Benzalkonium Chloride 5

TABLE 4 Formula for Carcinoma Component Component Weight (g) SodiumChloride (NaCl) 7 Agar 35 Sugar 220 Deionized water 700 BenzalkoniumChloride 3.5 Potassium Chloride (KCl) 1.9

TABLE 5 Formula for Pectoral Muscles Component Component Weight (g) Agar20 Sugar 360 Deionized water 900 Benzalkonium Chloride 4.14 Triton X-100Surfactant 20 Egg whites 50 Safflower oil 40

The exemplary components for the TMMs in Tables 1-5 were based onchoosing specific materials that have been modified and validated usingthe ionizing characteristic parameters as disclosed in Ruvio et al.,“Multimodal Breast Phantoms for Microwave, Ultrasound, Mammography,Magnetic Resonance and Computed Tomography Imaging,” Sensors, vol. 20,no. 8, Art. no. 8, Jan. 2020; Quan et al., “Characterization of adielectric phantom for high-field magnetic resonance imagingapplications,” Med. Phys., vol. 41, no. 10, Oct. 2014; Oglat et al.,“Chemical Items Used for Preparing Tissue-Mimicking Material ofWall-Less Flow Phantom for Doppler Ultrasound Imaging,” J. Med.Ultrasound, vol. 26, no. 3, pp. 123-127, 2018; Lafon et al., Aninnovative synthetic tissue-mimicking material for high-intensityfocused ultrasound. The Journal of the Acoustical Society of America,2001, 110(5), pp. 2613-2613; Manickam et al., “Development of a trainingphantom for compression breast elastography—comparison of variouselastography systems and numerical simulations,” J. Med. Imaging, vol.2, no. 4, Oct. 2015; Miyakawa et al., “Development of nonuniform breastphantom and its microwave imaging for tumor detection by CP-MCT,” 2009Annual International Conference of the IEEE Engineering in Medicine andBiology Society, Minneapolis, Minn., USA, 2009, pp. 2723-2726; andBrowne et al., “Tissue Mimicking Materials,” 20200170612, 4 Jun. 2020the entire disclosures of foregoing are incorporated herein byreference.

The structured tissues of the exemplary phantom concern the skin,fibro-glandular tissue, adipose tissue, pectoral muscle and carcinomawith new developed tissue mimicking materials (TMMs). The purpose of theTMMs was to match the response of the real breast tissues when appliedto ionizing and non-ionizing imaging modalities.

The tissue-mimicking materials were characterized for modalities utilizeionizing radiation such as computed tomography and mammography. The TMMsof the exemplary phantoms were characterized analytically by using threeimportant parameters which were mass attenuation coefficient, electrondensity (n_(e)) and effective atomic number (Z_(eff)). Mass attenuationcoefficient describes how simply it can be penetrated by a beam oflight, sound, particles, or other energy or matter as described inHubell et al., “X-Ray Mass Attenuation Coefficients,” NIST,https_://www.nist.gov/pml/x-ray-mass-attenuation-coefficients the entiredisclosure is incorporated herein by reference. While the electrondensity measures the electron probability of existing in a unit volumeof an element as disclosed in Khan et al., Khan's the physics ofradiation therapy, Fifth edition. Philadelphia, Pa.: Lippincott Williams& Wilkins/Wolters Kluwer, 2014., the entire disclosure is incorporatedherein by reference. Z_(eff) is an element atomic number in whichphotons interact similar to a given composite material. It was foundnumerically by using National Institute of Standards and Technology(NIST) XCOM. The energies were specified according to the range used ineach imaging modality after having the weight fractions for each tissuecompounds.

From the mass density (μ_(m)) and atomic composition (z/A), the electrondensity of a material can be calculated according to the formula:

n _(e)=ρ_(m) ·N _(A)·(z/A)  (1)

where:z/A=Σ _(i) a _(i)(z _(i) /A _(i))  (2)

N_(A) is Avogadro's number and a_(i) is the fraction by weight of theith element of atomic number Z_(i) and atomic weight A_(i) ranging from0 to 8 depending on the elemental composition.

Z_(eff) can be obtained from:

Z _(eff)(Σ_(all tissue components(n)) a _(n) Z _(n)^(2.94))^(1/2.94)  (3)

Where a_(n) represent the fractional contribution of each element to thetotal number of electrons in mixture.

Based on the International Commission on Radiation Units (ICRU),reference values elemental composition weight fractions of the realtissues were compared and validated with the above calculations.

The weight fractions of the exemplary TMMs elements were calculated foreach breast tissue of skin, fibro-glandular, adipose, pectoral muscle,and malignant carcinoma. Table 6 presents the resulted weight fractionsof TMMs comparable to the real breast tissue elemental compositionsweight fractions found from ICRU reports. The values were close to thereal especially when focusing on the main tissue elements which are C, Hand O for all tissues.

Table 7 was developed based on Equations (1) and (2) which present thespecific tissue electron density and effective atomic number. Low errorswere observed with maximum of 5.76% for fibro-glandular Z_(eff) andminimum of 0.00415% for pectoral muscle n_(e). That means the exemplarymaterials and quantities can produce similar real breast tissueinteractions when exposed to ionizing radiations with energies in therange 10-150 KeV.

In some embodiments, the skin mimicking segment has an electron density(n_(e)) of 3.59E+23 −3.61E+23 e⁻/g, preferably about 3.60 E+23 e⁻/g, andan effective atomic number (Z_(eff)) of 7.2-7.3, preferably about 7.22.

In some embodiments, the adipose tissue mimicking segment has anelectron density (n_(e)) of 3.17E+23 −3.20E+23 e⁻/g, preferably about3.20 E+23 e⁻/g, and an effective atomic number (Z_(eff)) of 6.3-6.4,preferably about 6.33.

In some embodiments, the fibro-glandular tissue mimicking segment has anelectron density (n_(e)) of 3.15E+23 −3.45E+23 e⁻/g, preferably about3.18 E+23 e⁻/g, and an effective atomic number (Z_(eff)) of 6.9-7.4,preferably about 6.93.

In some embodiments, the pectoral muscle mimicking segment has anelectron density (n_(e)) of 3.40E+23 −3.5E+23 e⁻/g, preferably about3.44 E+23 e⁻/g, and an effective atomic number (Z_(eff)) of 8.1-8.3,preferably about 8.18.

In some embodiments, the carcinoma mimicking segment has an electrondensity (n_(e)) of 3.25E+23 −3.65E+23 e⁻/g, preferably about 3.57 E+23e⁻/g and an effective atomic number (Z_(eff)) of 7.1-7.5, preferablyabout 7.11.

FIGS. 4, 5, 6, 7 and 8 show the mass attenuation coefficient against theapplied photonic energy for the exemplary skin, adipose tissue,fibro-glandular tissue, malignant carcinoma, and pectoral musclestissues, respectively for both real ICRU elemental compositions and thephantom calculated elemental compositions. All the introducedtissue-mimicking materials of the exemplary phantom revealed a goodagreement in all the energy range of energy with insignificantdifferences in the range of small applied photonic energy. The massattenuation coefficient for the skin and adipose tissue real andcalculated results showed a great overlapped graph for all points withhigh similarity.

In some embodiments, the heterogeneous breast implant simulates thebreast tissue under a medical imaging technique, such as computedtomography (CT), magnetic resonance imaging (MRI), ultrasonography, andX-ray imaging.

In preferred embodiments, the medical imaging technique is magneticresonance imaging (MRI), computed tomography scan (CT scan), or both.

The exemplary phantom revealed excellent ionizing radiation propertiesas the real breast tissues. These properties were the effective atomicnumber (Z_(eff)), electron density (n_(e)) and mass attenuationcoefficient (MAC). Moreover, the T1 and T2 relaxation times of the TMMsexhibited excellent agreement with the real breast tissues when examinedat a magnetic resonance imaging (MM) laboratory at 0.5 Tesla. Thefabricated breast phantom was tested using computed tomography (CT) andMM machines, and the scanned images were in excellent agreement with thereal tissues when examined using these machines. The TMMs of the presentdisclosure provide the same breast tissues ionizing radiation properties(reflection coefficient, electron density, and effective atomic number)when exposed to X-rays in CT, Radiographic and Mammographic imagingmodalities.

Two exemplary carcinoma TMMs of 2-cm. diameter were inserted in thebreast, and they appeared clearly in the CT scanned images. The twocarcinoma TMMs were modeled as malignant water content tissues and thusthey appeared dark when T1-We−/ghed image contrast technique is used inMM and bright when T2-Weighted image contrast technique is used. Theachieved results were in great agreement with the real water contentcarcinoma tissues when examined with MM using T1W and T2W, as shown inTable 8. Measurements of T1 and T2 relaxation times of exemplary TMMsare shown in FIG. 10 .

TABLE 6 Breast Phantom Elemental Compositions Weight Fractions Tissue NaCl C H O Mg Skin Phantom 0.004821033 0.007692516 0.275323873 0.0984872580.613573165 — ICRU 0.001 0.003 0.204 0.1 0.645 — Adipose Phantom0.000832225 0.004552743 0.689825033 0.12133871 0.17621494 — ICRU 0.0010.001 0.598 0.114 0.278 — Fibrogla- Phantom — 0.002619926 0.2188206180.105858707 0.659929689 — ndular ICRU 0.001 0.001 0.332 0.106 0.527 —Pectoral Phantom — 0.000234935 0.16631 0.096804967 0.73072 — MusclesICRU 0.0008 — 0.123 0.101997 0.720993 0.002 Carcinoma Phantom0.002849483 0.005615315 0.116584436 0.098753539 0.776084016 — ICRU — —0.187626775 0.101419878 0.668356998 — Breast Phantom ElementalCompositions Weight Fractions Tissue K N S P Si Al Skin Phantom —0.000102156 — — — — ICRU 0.001 0.042 0.002 0.001 — — Adipose Phantom0.003605935 — — — 0.003630414 — ICRU — 0.007 0.001 — — — Fibrogla-Phantom 0.002477372 0.000147657 — — 0.002646044 0.007499987 ndular ICRU— 0.03 0.002 0.001 — — Pectoral Phantom — 0.005929387 — — — — MusclesICRU 0.0002 0.035 0.005 0.002 — — Carcinoma Phantom 0.0010311310.000113212 — — — — ICRU — 0.042596349 — — — —

TABLE 7 Skin, Fibro-glandular, Adipose, Pectoral Muscles and CarcinomaElectron Density and Z_(eff). Electron Tissue density Error % Z_(eff)Error % Skin Phantom 3.59776E+23 0.163 7.22 0.558 ICRU 3.60362E+237.2630298 Adipose Phantom   3.39E+23 0.0315 7.33E+00 5.76 ICRU3.17967E+23 6.93E+00 Fibroglandular Phantom 3.19937E+23 0.6196.391046106 0.956 ICRU 3.17967E+23 6.330516684 Pectoral Phantom  3.43E+23 0.00415 8.29E−01 0.195 Muscles ICRU   3.44E+23 8.184042E−1   Carcinoma Phantom   3.57E+23 2.93 7.46E+00 4.46 ICRU   3.31E+23 7.11E+00

TABLE 8 Comparing real and measured (T1, T2) for adipose and pectoralmuscle tissues. T1 T2 Measured Measured Tissue Real (0.5 T) (0.5 T) Real(0.5 T) (0.5 T) Adipose tissue 0.102 s [49] 0.131 s 0.08 s [49] 0.082 sPectoral muscle 0.560 s [49] 0.586 s 0.034 s [49] 0.053 s

The TMMs of the present disclosure have substantially the same T1 and T2relaxation times of real breast tissues when exposed to static magneticfields of 0.5 T and 1.5 T and in the existence of a rotating field. TheTMMs can therefore also be used effectively in MRI.

Additionally, the mass attenuation coefficients in cm²/g of theexemplary phantom tissues were found and plotted against the real breasttissues mass attenuation coefficients in the energy range of 10 KeV to150 KeV, as clinically used in mammography and CT machines.

A particularly preferred embodiment of the invention includes referencepoints or target areas, e.g., gelled point, having different gelationcharacteristics than any of the adipose tissue mimicking, afibro-glandular tissue mimicking and pectoral muscle mimicking segments.These gelled points can be formed by the inclusion of a gelling agent,preferably pectin, or a cross-linking agent such as an alkali metal saltduring fabrication. Gelled points represent portions of the breastphantom in which the density of the material is different from itsimmediate surroundings. Gelled points can function as training aids oras a means of determining distance in the three-dimensional breastphantom structure. Gelled points preferably have a diameter dimension of0.5-2.0 mm, preferably 1.0-1.5 mm. The dimension may be determined byx-ray, CT or MRI where the outer limit of gelling point represents aportion of the phantom composition having an absorption of at least 90%preferably 95% the value of the absorption of the phantom tissuemeasured at a portion of the breast phantom that is separate from thegelled point, for example separated from the center point of the gelledpoint by a distance of 5 mm, preferably 10 mm. In this respect thegelled points have a gradient characteristic with greatest density atthe center point decreasing outwardly from the center point. Preferablythe density of the gelled points is at least 5% greater than the densityof the surrounding fence and tissue, preferably at least 7.5% or atleast 9% greater. In another preferred embodiment, the breast phantomincludes a plurality of gelled points equidistantly spaced within aplane of the breast phantom. For example, four gelled points mayrepresent a bottom or horizontal plane through the breast phantom. Avertical plane that may share one or more gelled points with thehorizontal plane but also includes at least four gelling points is alsopresent. The vertical and horizontal planes are preferably perpendicularto one another although embodiments in which the planes are at an angleother than 90° are possible such as 45°, 60° or 85°. The gelled pointstypically represent less than 5% of the weight total weight of breastphantom, preferably less than 2%, less than 0.5% or less than 0.05% ofthe total weight of the breast phantom.

In yet another embodiment, referring to FIG. 13 , a method 100 ofproducing the heterogeneous breast phantom is provided wherein themethod 100 comprises, at step 102, casting a first composition thatcomprises polyvinyl alcohol and sugar to a skin-shaped mold, therebyforming the skin mimicking segment; at step 104, casting a secondcomposition that comprises beeswax to an adipose tissue-shaped mold,thereby forming the adipose tissue mimicking segment; at step 106,casting a third composition that comprises glycerol to a fibro-glandulartissue-shaped mold, thereby forming the fibro-glandular tissue mimickingsegment; at step 108, casting a fourth composition that comprises sugarand optionally comprises egg whites to a pectoral muscle-shaped mold,thereby forming the pectoral muscle mimicking segment; at step 110,casting a fifth composition that comprises sugar to a carcinoma-shapedmold, thereby forming the carcinoma mimicking segment; and, at step 112,arranging the segments to produce the heterogeneous breast phantom suchthat the phantom represents a breast tissue. FIG. 9 shows exemplarymethods for fabrication of TMMs.

In some embodiments, the method 100 of producing the heterogeneousbreast phantom is provided wherein at least one of the molds is producedvia 3D printing. Alternatively, the molds may be produced by processingtechniques such as extrusion, co-extrusion, injection molding, blowmolding, vacuum forming, thermos-forming, elasto-welding, pultrusion,compression molding, and other fabrication techniques. An exemplaryfabricated breast phantom is shown in FIG. 11 . The validation of anexemplary phantom using CT and breast MRI machines is shown in FIG. 12 .

MATERIALS AND METHODS Definitions of Terms

n_(e)=Electron Density

Z_(eff)=Effective atomic number

From the mass density (ρ_(m)) and atomic composition (z/A), the electrondensity of a material can be calculated according to the formula:

n _(e)=ρ_(m) ·N _(A)·(z/A)  (1)

where:z/A=Σ _(i) a _(i)(z _(i) /A _(i))  (2)

N_(A) is Avogadro's number and a_(i) is the fraction by weight of thei^(th) element of atomic number Z_(i) and atomic weight A_(i) rangingfrom 0 to 8 depending on the elemental composition.

Z_(eff) can be obtained from:

Z _(eff)(Σ_(all tissue components(n)) a _(n) Z _(n)^(2.94))^(1/2.94)  (3)

where a_(n) represent the fractional contribution of each element to thetotal number of electrons in mixture.

A. Patient Data Acquisition

Institutional Review Board (IRB) approval was obtained from King FandSpecialist Hospital (KFSH) in Saudi Arabia, Dammam (RAD0319), in orderto use patient data. A Digital Imaging and Communications in Medicine(DICOM) magnetic resonance imaging (MM) breast image with dynamiccontrast-enhancement is used. The criteria of patient data selectionwere built upon the BI-RADS which was established by American College ofRadiology (ACR). The score of the chosen image was I (normal breast)with dense fibro-glandular tissues to be inserted with a malignantlesion.

B. Image Segmentation and Creation of Molds

For breast tissue segmentation, the acquired MR breast images wereimported into segmentation software. This was to have a realisticseparated geometry for the external shape, skin, fibro-glandular tissueand tumor. The patient DICOM images were imported into 3D slicersoftware with 128 slices for internal tissues segmentation to segmentout the skin and fibro-glandular tissue from the surrounding adipose.The purpose was to ensure a complete elimination of all the surroundingstructures. Each slice was segmented in different orientations toimprove segmentation reliability using the threshold function, which wasadjusted manually. Afterwards, the segmented fibro-glandular tissue wasconverted into 3D model and saved as Standard Triangle Language (STL)file for further processing. Negative and positive molds were createdfrom the segmented skin layer to create a single flask for the skin andadipose tissue. Segmented fibro-glandular was modified to create a basefor handling purposes. Segmented fibro-glandular was modified to createa base for handling purposes. Also, a tumor mold of 2 cm diameter wascreated. The molds of the external breast shape, skin, andfibro-glandular were printed using acrylonitrile butadiene styrene (ABS)plastic to have a high realistic distribution of the interior structure,specifically for the fibro-glandular mold as described in Burfeindt etal., “MM-Derived 3-D-Printed Breast Phantom for Microwave Breast ImagingValidation,” IEEE Antennas Wirel. Propag. Lett., vol. 11, pp. 1610-1613,2012, the entire disclosure is incorporated herein by reference.

Image Segmentation

For the patient DICOM images segmentation to extract the region ofinterest (ROI) through detection of boundaries, breast outer shape andfibro-glandular tissue was separated from other surrounding tissuesusing 3D Slicer software to have a realistic separated geometry for theexternal shape, skin and fibro-glandular tissue. The resulted 3Dfibro-glandular volume model comparable to the axial and coronal imagesslices with high anatomical precision shown in FIGS. 1A-1D fromdifferent perspectives. The segmented model presented a need for furthersmoothing and processing to be able for 3D printing without defects.

3D Mold Fabrication

Free-floating and deformities were removed, and model hollows wereedited during this process. The skin was converted into a negative moldto represent the outer shape of the phantom. In this outer shape mold, a3 mm thickness was added at the rounded corners to create the skintissue thickness. The fibro-glandular STL file was edited to have anapplicable adipose to fibro-glandular interface surface for printing.FIG. 2 presents all processed molds.

The 3D models of the phantom were printed in Namthaja 3D printingmanufacturing solutions, Saudi Arabia, Dammam. The printed externalshape, skin, fibro-glandular, and tumor molds are shown in FIG. 3 .

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described herein.

1: A heterogeneous breast phantom, comprising: a skin mimicking segmentthat comprises polyvinyl alcohol and sugar; an adipose tissue mimickingsegment that comprises beeswax; a fibro-glandular tissue mimickingsegment that comprises glycerol; and a pectoral muscle mimicking segmentthat comprises sugar and optionally comprises egg whites, wherein eachsegment is shaped and arranged such that the breast phantom represents abreast tissue. 2: The heterogeneous breast phantom of claim 1, furthercomprising a carcinoma mimicking segment that comprises sugar. 3: Theheterogeneous breast phantom of claim 2, wherein each segment furthercomprises water, a vegetable oil, a surfactant, and agar. 4: Theheterogeneous breast phantom of claim 3, wherein the vegetable oil issafflower oil. 5: The heterogeneous breast phantom of claim 3, whereinthe surfactant is a nonionic surfactant. 6: The heterogeneous breastphantom of claim 2, wherein the skin mimicking segment, the adiposetissue mimicking segment, the fibro-glandular tissue mimicking segment,and the carcinoma mimicking segment each further comprise at least onetype of scattering particles selected from the group consisting of NaCl,KCl, Al₂O₃, and SiC particles. 7: The heterogeneous breast phantom ofclaim 1, wherein polyvinyl alcohol and sugar are present in the skinmimicking segment in amounts of 4-6 wt % and 27-35 wt %, each relativeto a total weight of the skin mimicking segment. 8: The heterogeneousbreast phantom of claim 1, wherein beeswax is present in the adiposetissue mimicking segment in an amount of 38-45 wt % relative to a totalweight of the adipose tissue mimicking segment. 9: The heterogeneousbreast phantom of claim 1, wherein glycerol is present in thefibro-glandular tissue mimicking segment in an amount of 10-15 wt %relative to a total weight of the fibro-glandular tissue mimickingsegment. 10: The heterogeneous breast phantom of claim 1, wherein sugaris present in the pectoral muscle mimicking segment in an amount of22-28 wt % relative to a total weight of the pectoral muscle mimickingsegment, and wherein egg whites, if present, are present in an amount of2-8 wt % relative to a total weight of the pectoral muscle mimickingsegment. 11: The heterogeneous breast phantom of claim 2, wherein sugaris present in the carcinoma mimicking segment in an amount of 20-25 wt %relative to a total weight of the carcinoma mimicking segment. 12: Theheterogeneous breast phantom of claim 1, wherein the skin mimickingsegment has an electron density (n_(e)) of 3.59E+23 −3.61E+23 e⁻/g andan effective atomic number (Z_(eff)) of 7.2-7.3. 13: The heterogeneousbreast phantom of claim 1, wherein the adipose tissue mimicking segmenthas an electron density (n_(e)) of 3.17E+23 −3.20E+23 e⁻/g and aneffective atomic number (Z_(eff)) of 6.3-6.4. 14: The heterogeneousbreast phantom of claim 1, wherein the firbo-glandular tissue mimickingsegment has an electron density (n_(e)) of 3.15E+23 −3.45E+23 e⁻/g andan effective atomic number (Z_(eff)) of 6.9-7.4. 15: The heterogeneousbreast phantom of claim 1, wherein the pectoral muscle mimicking segmenthas an electron density (n_(e)) of 3.40E+23 −3.5E+23 e⁻/g and aneffective atomic number (Z_(eff)) of 8.1-8.3. 16: The heterogeneousbreast phantom of claim 2, wherein the carcinoma mimicking segment hasan electron density (n_(e)) of 3.25E+23 −3.65E+23 e⁻/g and an effectiveatomic number (Z_(eff)) of 7.1-7.5. 17: The heterogeneous breast phantomof claim 1, which simulates the breast tissue under a medical imagingtechnique. 18: The heterogeneous breast phantom of claim 17, wherein themedical imaging technique is magnetic resonance imaging (MRI), computedtomography scan (CT scan), or both. 19: A method of producing theheterogeneous breast phantom of claim 2, the method comprising: castinga first composition that comprises polyvinyl alcohol and sugar to askin-shaped mold, thereby forming the skin mimicking segment; casting asecond composition that comprises beeswax to an adipose tissue-shapedmold, thereby forming the adipose tissue mimicking segment; casting athird composition that comprises glycerol to a fibro-glandulartissue-shaped mold, thereby forming the fibro-glandular tissue mimickingsegment; casting a fourth composition that comprises sugar andoptionally comprises egg whites to a pectoral muscle-shaped mold,thereby forming the pectoral muscle mimicking segment; casting a fifthcomposition that comprises sugar to a carcinoma-shaped mold, therebyforming the carcinoma mimicking segment; arranging the segments toproduce the heterogeneous breast phantom such that the phantomrepresents a breast tissue. 20: The method of claim 19, wherein at leastone of the molds is produced via 3D printing.